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8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation
1 Department of Cell Biology, The Scripps Research Institute, La Jolla, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
2 Institut Jacques Monod, University Paris VII, Paris, France
*Author for correspondence (e-mail: gong{at}scripps.edu)
Accepted 3 October 2001
The development of the vertebrate lens utilizes a sophisticated cell-cell communication network via gap junction channels, which are made up of at least three connexin isoforms, 
8 (Cx50), 3 (Cx46) and 1 (Cx43), and which are encoded by three different genes. In a previous study, we reported that, with a disruption of Gja3 (3 connexin), mice developed nuclear cataracts with a normal sized lens. We show that Gja8tm1 (8–/–) mice develop microphthalmia with small lenses and nuclear cataracts, while the 8 heterozygous (+/–) mice have relatively normal eyes and lenses. A comparative study of these 3 and 8 knockout mice showed that the protein levels of both 3 and 8 were independently regulated and there was no compensation for either the 3 or 8 protein from the wild-type allele when the other allele was disrupted. More interestingly, western blotting data indicated that the presence of 8 in the lens nucleus is dependent on 3 connexin, but not vice versa. The staining of the knock-in lacZ reporter gene showed the promoter activity of 8 connexin is much higher than that of 3 connexin in embryonic lenses and in adult lens epithelium. More importantly, a delayed denucleation process was observed in the interior fibers of the 8–/– lenses. Therefore, 8 connexin is required for proper fiber cell maturation and control of lens size.
Key words: Connexin, Lens, Microphthalmia, Cataract, Mouse
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